Cutaneous Delayed Hypersensitivity Reactions Research Articles

Atopy Associated With Positive Patch Test and Possible Allergic Contact Dermatitis

Atopy is a genetic predisposition to the development of allergic reactions and the increased production of immunoglobulin E (IgE) upon exposure to environmental antigens. Clinical manifestations of atopy include asthma, atopic dermatitis (AD), and allergic rhinoconjunctivitis (ARC). To determine if cutaneous delayed hypersensitivity reactions (CDHRs) as assessed by patch testing are higher among patients with a history of atopy and with a familial predisposition to atopy. For this study, we reviewed the patch test database of the UBC Contact Dermatitis Clinic over a 4-year time span. A personal history of asthma, AD, and ARC was recorded. In addition, a family history was obtained and manifestations of atopy in family members were noted. A total of 1515 patients were included in this study. Our data show that the odds ratio (OR) of a positive patch test with a personal history of atopy was 1.39, while the OR of a positive patch test with a family history of atopy was 1.69. Conversely, a personal history of respiratory atopy did not significantly affect the probability of a positive patch test, with an OR of 1.03. We conclude from our study that patients with a personal or family history of atopy have an increased risk of allergic contact dermatitis (ACD). These results provide further evidence for the link between atopy and ACD and suggest that children of atopic parents should avoid potential contact allergens and would likely benefit from prophylactic emollient use.

Hypersensitivity reactions to heparins.

This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients. Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives. Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.

Immunological Effects of Total Flavones from Leaves of Choerospondias axillaris on Mice

Abstract Objective To investigate the effect of total flavones from the leaves of Choerospondias axillaris (TFLCA) on the immune function of normal mice and to provide the experimental basis for the reasonable application of C. axillaris. Methods The carbon clearance method, cutaneous delayed hypersensitivity reaction method, serum hemolysin method, and index of immune organs were used to study the effect of TFLCA on the immune function of mice. Results TFLCA could enhance the phagocytic function of mononuclear macrophage and the cutaneous delayed hypersensitivity reaction of mice, and increase the content of hemolysin antibody and the thymus index in mice. Conclusion TFLCA could improve the celiac macrophage activity and specific immunity of mice, and TFLCA, consisting with the total flavones of Choerospondiatis Fructus (TFCF), has the effect on the immune function of mice. So both TFLCA and TFCF have the regulatory effects on the immune function of mice.

Immunological Study of Non Immediate Allergic Reaction to Infliximab

RATIONALE: Infliximab is a chimeric monoclonal antibody against TNF-α extensively employed in the therapy of rheumatoid arthritis. Hypersensitivity reactions to this drug, both acute and delayed infusion reactions have been described. Cutaneous delayed hypersensitivity reactions are rare, and the underlying pathomechanisms have not been studied and a T cell involvement has not been achieved. We present two patients with delayed skin eruptions after infliximab administration where a T-cell mechanism has been demonstrated.

Differential gene expression in drug hypersensitivity reactions: induction of alarmins in severe bullous diseases

Delayed hypersensitivity reactions to drugs can be life-threatening and constitute a growing problem in clinical practice. Although drug-specific T cells seem to be involved, the cellular and molecular bases of their aetiopathology are not fully understood. To study the molecular mechanisms underlying the pathogenesis and the clinical heterogeneity of cutaneous delayed hypersensitivity reactions to drugs. We characterized the gene expression profiles of peripheral blood mononuclear cells (PBMCs) isolated from patients during the acute phase of the reaction and upon resolution of clinical symptoms using a cDNA array technology. Low-density arrays were used to confirm differential expression of selected genes during the acute disease in patients and to compare gene expression in patients and exposed control donors by quantitative real-time polymerase chain reaction. Eighty-five genes were found to be differentially expressed during the acute phase of cutaneous drug-induced delayed hypersensitivity reactions. Furthermore, 92 genes with distinct expression patterns in severe and benign diseases during the acute phase were identified. PBMCs from patients with severe bullous diseases showed a characteristic gene expression pattern with lower expression of genes encoding T cell-specific proteins and high expression of cell cycle-related genes and genes coding for inflammatory-related mediators among which several endogenous damage-associated molecular patterns (DAMPs) or alarmins were found. Distinct gene expression profiles in PMBCs define benign and severe clinical entities. Overexpression of endogenous DAMPs in Stevens-Johnson syndrome and toxic epidermal necrolysis suggest that drugs can trigger the alarmin system in sensitized patients leading to life-threatening diseases.

Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment.

A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cells and CD3+TCR gamma delta + cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.

Induction of cutaneous delayed hypersensitivity reactions in mice sensitized with intragastrically administered hapten: activation of Langerhans cells in the sensitization and elicitation phases.

As seen in atopic dermatitis, allergic diseases often produce lesions both in the gastrointestinal tract and the skin, suggesting the involvement of an immunological relationship between the two organs in the pathogenesis. To study the role of gastric and epidermal Langerhans cells (LCs) in the sensitization and elicitation phases, respectively, of cutaneous delayed-type hypersensitivity (DTH) reactions to intragastrically administered hapten. BALB/c mice, which were subjected to intragastric administration of trinitrochlorobenzene 5 days previously, received an elicitative challenge of the same hapten to the ear skin. Sections of the ear were immunostained for CD4 and CD8. Epidermal sheets of the ear and epithelial sheets of the forestomach were immunostained for I-A and observed under a confocal laser scanning microscope. Cutaneous DTH reactions were induced in mice, as demonstrated by an increase in ear thickness and a prominent infiltration of CD4+ and CD8+ lymphocytes at 24-36 h after the elicitative challenge. In the elicitation phase, epidermal LCs showed a significant increase in size, indicating in vivo activation, at 24 h. In the sensitization phase, gastric LCs increased in size at 2 h, became round at 6 h, and decreased in number at 24 h, possibly representing the sequential events of LC activation and migration from the epithelium. The present study demonstrated that gastric LCs and epidermal LCs were activated in vivo in the sensitization and elicitation phases, respectively, of cutaneous DTH reactions in orally sensitized mice.

Tumor cell-based vaccination in renal cell carcinoma: rationale. approaches, and recent clinical development.

Since there is some evidence for spontaneous immunity against renal cell carcinoma, vaccination strategies are often used in patients with this tumor type, both in the adjuvant and the metastatic setting. Therefore, therapeutic strategies aim at augmenting anti-tumor immunity, but tumor-specific antigens suitable for vaccination purposes in renal cell carcinoma still remain to be identified. Early approaches used whole tumor cells or cell lysates with or without non-specific adjuvants like BCG. Studies investigating tumor cell vaccines have demonstrated immunological responses following vaccination, like positive cutaneous delayed hypersensitivity reactions indicating biological acitivity of tumor cell vaccines, and clinical responses have been observed as well. However, no clinical benefit has been demonstrated in randomized phase III trials. In recent years, efforts to develop more potent vaccines resulted in more sophisticated methods of tumor vaccination: The insertion of "neo-antigens" to enhance immunogenicity, the insertion of T-cell co-stimulatory molecules to enhance anti-tumor T-cell activation and the local production of cytokines to enhance T-cell function or the migration of antigen-presenting cells. Tumor cells have been genetically modified to express and produce cytokines, which in turn enhance the immunogenicity of the vaccine. The important role of dendritic cells has been recognized and tumor antigen-pulsed dendritic cells have been proposed. Hybrid cell vaccines are another promising approach. Safety and some effectiveness of these vaccines were demonstrated in phase I and II trials. However, randomized phase III trials are mandatory to confirm the usefulness of vaccination strategies. This review will describe the principals of tumor vaccination and, in a second part, focus on clinical studies of tumor vaccination in patients with renal cell carcinoma.

Extracellular matrix proteins in organ transplantation.

Extracellular matrix proteins in organ transplantation.

Endothelial Cells Implicated in Delayed Hypersensitivity Reactions

The pathogenesis of cutaneous delayed hypersensitivity reactions is not yet fully understood. While circulating lymphocytes and their resultant

Loss of Cutaneous Delayed Hypersensitivity Reactions in Nevus Anemicus

The relationship of adhesion molecules in the dermis to immunologically mediated cutaneous inflammation can be understood by focusing on a serendipitous phenomenon: a lack of dermatitis within the margins of a nevus anemicus (NA) in generalized contact dermatitis. The expression and induction of endothelial and epithelial adhesion molecules with intradermally injected cytokines were investigated. Nevus anemicus without dermatitis lacked histopathological changes consistent with inflammatory cellular infiltration. The surrounding skin of the dermatitic lesion expressed HLA-DR, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin on endothelial cells, and HLA-DR and ICAM-1 in the epidermis. However, the skin of the NA lacked endothelial E-selectin and epidermal HLA-DR and ICAM-1 expression. Interferon gamma, injected intradermally, induced endothelial and epidermal HLA-DR and ICAM-1 expression in the NA and surrounding normal skin. While interferon gamma strongly induced E-selectin expression on endothelial cells in normal skin, it failed to induce endothelial E-selectin expression in the NA. This study suggests that vessels in the NA do not respond normally to proinflammatory cytokines, at least at the level of E-selectin expression. The absence of keratinocyte ICAM-1 and HLA-DR expression in the NA lesion in contact dermatitis is likely caused by the absence of infiltrating lymphocytes, rather than by the intrinsic unresponsiveness of keratinocytes to interferon gamma. Among the endothelial cell adhesion molecules in delayed hypersensitivity, E-selectin appears to be indispensable in recruiting circulating T lymphocytes to the skin.

The role of E-selectin in lymphocyte and polymorphonuclear cell recruitment into cutaneous delayed hypersensitivity reactions in sensitized pigs.

We have studied the role of E-selectin in leukocyte accumulation into Ag-specific cutaneous delayed-type hypersensitivity reactions in pigs sensitized to the topical application of 2,4-dinitro-1-fluorobenzene or to the intradermal injection of bacillus Calmette-Guérin. The delayed-type hypersensitivity reactions were shown to be specific for the sensitizing Ag and characterized by the up-regulation of E-selectin, as demonstrated by the uptake of tracer 99mTc-labeled monoclonal anti-E-selectin mAb and entry of 51Cr-labeled PBL and (111)In-labeled polymorphonuclear cells (PMN). Intravenous injection of 5 mg/kg of a F(ab')2 preparation of a monoclonal anti-E-selectin Ab at peak times of leukocyte entry resulted in a significant inhibition of entry of both PMN and lymphocytes. The anti-E-selectin Ab inhibited PMN recruitment by 70 to 90% and lymphocyte recruitment by 50 to 60%. In comparison, an anti-CD18 treatment reduced PMN recruitment by 70 to 90% and lymphocyte recruitment by 60 to 70% in this model. These data confirm an important role for E-selectin in the recruitment of both PMN and lymphocytes to sites of immune-based dermal inflammation.

Experimental immunity toMicrosporum canisand cross reactions with other dermatophytes of veterinary importance

An inactivated, broad-spectrum dermatophyte vaccine was used to produce an active immunity in guinea-pigs against Microsporum canis. None of the vaccinates developed infection from a contact exposure challenge that produced clinical infections in 70% of the unvaccinated controls. Infection with M. canis induced antibody titres (ELISA) and delayed cutaneous hypersensitivity (DCH) reactions to itself as well as cross-reacting titres to Trichophyton equinum and T. mentagrophytes and DCH reactions to T. mentagrophytes; however vaccinated animals developed significantly higher antibody titres and DCH responses to all of these antigens than did non-vaccinated animals which had been infected or exposed. Rabbits hyperimmunized with culture filtrate antigens to single dermatophyte agents (M. canis, M. gypseum, T. equinum, and T. mentagrophytes) developed positive inter-species and inter-generic DCH cross-reactions to a battery of six skin test antigens (M. canis, M. gypseum, M. equinum, T. equinum, T. mentagrophytes var. mentagrophytes and T. verrucosum). Guinea-pigs vaccinated with a T. equinum vaccine had increased resistance to M. canis infection than did non-vaccinated controls. These findings support clinical observations which suggest establishment of a broad-based immunity in animals following infection with a single dermatophyte.

Cutaneous delayed hypersensitivity reactions of cattle vaccinated with mutant strains of Brucella abortus, using brucellins prepared from various brucellar strains

Summary Cutaneous reactivity to brucellin was evaluated in 10-month-old heifers vaccinated with low-virulence mutant strains of Brucella abortus and was compared with brucellin reactions in postparturient cows with active brucellosis. In the cows, the cutaneous lesion was characterized microscopically as severe, acute, serofibrinous vasculitis; dermal lesions at 6, 12, 25, and 48 hours after brucellin injection consisted of endothelial activation and perivascular exudation that led to progressive accumulation of fibrin, monocytes, macrophages, and lymphocytes. In vaccinated heifers, cutaneous tests were done, using standard brucellin, brucellin prepared from strain RB51, and the purified brucellar proteins-31K and superoxide dismutase. Negative-control cattle given saline solution, did not have cutaneous reactions. Standard brucellin induced the most marked reactions in vaccinated heifers. Brucellin from rough strain RB51 caused positive reactions in heifers vaccinated with strain 19, but reactions were variable in other groups. Skin lesions induced by purified superoxide dismutase and 31-kd proteins in vaccinated cattle were not acceptable for diagnosis. Marked variability of test responses in vaccinated cattle precludes field use of this test to determine vaccination status.

Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly. Humoral immune response enhancement by thymostimulin

In order to explore the humoral primary and secondary response to tetanus toxoid (TT), and to define the possible immunopotentiating effect of the thymic hormone thymostimulin, we studied 13 elderly people, selected according to the Senieur Eurage protocol, vaccinated against TT, an antigen never encountered before. Six of them were treated with thymostimulin before and during the immunization protocol. Specific anti-TT antibody level measurement and spectrotypic analysis were performed on the sera collected from the subjects at different times over the immunization protocol. In addition, spontaneous in vitro production of anti-TT antibodies as well as cutaneous delayed hypersensitivity reactions were also studied. Only one patient showed a detectable humoral immune response after the first immunization. After the booster, four of six thymostimulin-treated individuals, compared with only two of seven controls, showed in vivo anti-TT humoral response; at the same time, spontaneous anti-TT production was detected in peripheral blood mononuclear cells from five of six thymostimulin-treated individuals but only three of seven untreated controls. These differences were highly significant (p < 0.0001). In addition, only in thymostimulin-treated subjects were the levels of serum anti-TT antibodies 14, 21 and 28 days after the booster significantly (p < 0.05) higher than the baseline values. The spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and reverse blotting showed total agreement with the results from enzyme-linked immunosorbent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

A correlation between serum immunosuppressive acidic protein and altered immunocompetence in patients with brain tumours

The present investigation was conducted to document a correlation between the serum levels of immunosuppressive acidic protein (IAP) and depressed lymphocyte responsiveness to mitogens in vitro in patients with intracranial tumours, and to delineate the possible roles of IAP upon immunocompetence in these patients. It was thought that high concentrations of IAP present in the serum of brain-tumour patients may play a significant role in the immunosuppression seen in this patient population. The effect of IAP upon mitogen-stimulated lymphocyte function was evaluated by tritiated (3H)-thymidine incorporation. Lymphocytes from both 30 patients with intracranial tumours and 30 normal individuals were incubated for 90 hours in culture medium in the presence of three mitogens: phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Lymphocytes obtained from patients with brain tumours and cultured in autologous serum displayed a significant depression of 3H-thymidine incorporation, as was observed in previous studies. In addition, a significant suppression of mitogen-induced activation of the normal lymphocytes was demonstrated in the presence of allogeneic patients' serum and the percentage of inhibition was found significantly proportional to the IAP concentrations. Furthermore it was also demonstrated that increased levels of serum IAP could significantly correlate with two in vivo aspects of impaired cellular immunity: the decreased lymphocyte counts in the peripheral blood and diminished cutaneous delayed hypersensitivity reactions measured by purified protein derivative (PPD) skin test reactivity. On the other hand, an attempt was also made to investigate changes in humoral immunity and immunoglobulin concentrations were observed not to correspond to the serum IAP levels. These studies suggest a possible connection between serum IAP levels and altered cellular immune competence in brain-tumour patients.

Intercellular Adhesion Molecule Expression in the Evolving Human Cutaneous Delayed Hypersensitivity Reaction

Intercellular adhesion molecule-1 (ICAM-1), putatively expressed by antigen-presenting or target skin cells, is a ligand for the lymphocyte function-associated antigen (LFA-1) present on circulating lymphocytes. Immunohistochemistry of normal adult human skin using monoclonal antiserum to ICAM-1 demonstrated focal reactivity restricted to endothelium lining the dermal microvasculature. Delayed hypersensitivity responses elicited with dinitrochlorobenzene in the skin of the same subject were evaluated sequentially over a 96 h period using immunohistochemical and ultrastructural techniques. The first alteration observed consisted of mast cell degranulation within perivenular foci in the superficial dermis at 4 h after antigen challenge. Sparse superficial perivascular T-cell infiltrates were present by 24 h. Progressive staining for ICAM-1 was observed in microvascular endothelium and in dermal dendritic cells between 24 and 48 h. ICAM-1 expression was documented focally within the lower epidermis at 48 h and diffusely within the lower and upper epidermal layers at 96 h. ICAM-1 expression by keratinocytes was consistently associated with T-cell migration into the epidermis, whereas migration was never observed in the absence of ICAM-1 reactivity. Immunoelectron microscopy confirmed ICAM-1 to be exclusively present on endothelial cells, dermal dendritic cells, mononuclear cells, and keratinocytes, and permitted characterization of the patterns of membrane reactivity. ICAM-1 expression by epidermal cells appears to be closely linked to the progressive migration of T cells from the dermis into the epidermis that characterizes cutaneous delayed hypersensitivity.

Zinc nutriture and cell mediated immunity in institutionalized elderly.

This study examined the effects of increasing zinc nutriture on the cell mediated immune response of an institutionalized elderly population. A volunteer institutionalized population was identified and nutritional assessment consisting of weighed food intake record and anthropometric measurements was conducted. Zinc status and delayed cutaneous hypersensitivity (DCH) skin tests were administered to determine immune responsiveness. Subjects were supplemented with 15 mg zinc gluconate for 28 days, after which the zinc status and immune status of each subject were reassessed. Results indicated that dietary zinc intakes were inadequate in 67% of the test population. After supplementation, serum zinc levels increased significantly (p < .006), while results of the alkaline phosphatase test indicated no significant change. DCH reactions improved significantly (p < .034) after zinc supplementation.

The effects of immunosuppression and anticoagulation on fibrin deposition and swelling in rat cardiac allografts

Rat cardiac allograft recipients were injected with radiolabeled human fibrinogen at intervals after transplantation. There was a progressive increase in tracer accumulation within graft ventricles, peaking at the time of rejection at about 30-fold that within syngeneic grafts. Protein extraction experiments indicated that ca. 90% of tracer was present as cross-linked fibrin at the time of rejection. Exudation within rejecting allografts was nearly threefold that in syngeneic grafts. The weight of allografts at different times after transplantation increased in close concordance with fibrin deposition. Pharmacologically immunosuppressed recipients showed negligible fibrin deposition and swelling whereas “B” rats and thoracic-duct-lymph-drained recipients showed moderate allograft swelling in the absence of significant fibrin deposition or rejection. The decreased fibrin deposition was not a result of depressed plasma clotting factor levels. B rats reconstituted with thoracic duct lymphocytes still had reduced allograft fibrin deposition in the presence of normal amounts of swelling and exudation. The anticoagulants warfarin and heparin greatly decreased allograft fibrin but were almost without effect on allograft swelling, exudation, and rejection. The possible participation of infiltrating macrophages in allograft fibrin deposition is discussed. Unlike cutaneous delayed hypersensitivity reactions, normal amounts of fibrin deposition appear not to be essential for full cardiac allograft rejection.

The acquired immunodeficiency syndrome (AIDS).

This article discusses clinical, immunologic, and etiologic considerations in the acquired immunodeficiency syndrome (AIDS) and the relationship of AIDS to other immunodeficiency diseases. The outstanding clinical feature of AIDS is the occurrence of opportunistic infections in individuals with no prior known cause of immunodeficiency. Such infections have included Pneumocystis carinii, oral thrush from Candida albicans, cytomegalovirus, atypical mycobacteria, cryptosporidium, and Herpes simplex virus. Central nervous system invasion by Cryptococcus neoformans and Toxoplasma gondi has also been reported. Persistent quantitative and functional depression of T4 cells is the immunologic hallmark of full-blown AIDS. Another prominent feature is in vitro spontaneous hyperactivity of B cells. AIDS patients lose cutaneous delayed hypersensitivity reactions both to recall and to new antigens, and T-cell-mediated cytotoxicity is diminished. The mounting number of T8 cells and diminution in T4 cells causes an inversion in the normal T4:T8 ratio. It has been hypothesized that the host defense mechanism is the attempt of the cytotoxic T8 cells to destroy the virus-infected T4 cells. 2 groups of investigators have discovered a lymphocytotropic retrovirus from blood and node lymphocytes of AIDS patients: lymphadenopathy-associated virus (LAV) or human T-lymphotropic virus type III (HTLV-III). Among the primary immunodeficiencies, AIDS most closely resembles the defect observed in purine nucleoside phosphorylase deficiency, an inherited autosomal recessive phenomenon. There is evidence that multiple infections or antigen overload characterize all the risk groups for AIDS. Moreover, antigen overload in experimental animals and man has been shown to suppress immune responses and to down-regulate Ia antigen expression on monocytes. This may prove to be a necessary precondition for the development of AIDS.